Within the last two decades, a series of novel therapeutic nucleic acids entered research and clinical evaluation. Their differences both in biophysical properties as well as in mode and site of biological action provide polymer-based carriers with new delivery challenges. Recent tailor-made designs of polymeric carriers are reviewed that were optimized for nucleic acid cargos such as plasmid DNA, siRNA, and micro RNA, mRNA, or genome-modifying nucleic acids. The specific requirements for the various therapeutic cargos are discussed. Future directions include dynamic bioresponsive polymers as components of nanomachines, multifunctional sequence-defined carriers for evolution-based selective optimization, and organic inorganic multicomponent nanoassemblies.